ETIOPATHOGENESIS OF BEHCET'S SYNDROME: RECENT DEVELOPMENTS AND CURRENT CONTROVERSIES

Abstract

Genetic, infectious and immune dysfunctions are implicated in the etiopathogenesis of Behget’s Syndrome (BS). Histopathological studies reveal mixed cellular infiltrations consisting of mostly T lymphocytes, monocyte-macrophages and neutrophils. Although a viral etiology is also suggested, atypical streptoccocci (Strep Sanguis, Salivarius etc) is the most investigated. Increased pro- inflammatory and Th1 type cytokines such as TNF-a, IFN-y, IL-2, IL-6 and IL-8 are found to be increased in the sera and in vitro culture supernatants. A controversial point is whether neutrophils are primarily defective (hyper-reactive) or activated due to the cytokine profile. Streptoccocal proteins such as KTH-1 or 65 kD mycobacterial heat shock protein (HSP) and its cross-reactive human homologue are shown to cause T and B cell responses in patients with BS. Both CD4+ and y8 T cells are activated with antigen-specific oligoclonal expansions and increased secretions of IFN-y, IL-8 and TNF-a. The link with HLA-B51 which is present as a susceptibility or a severity marker of BS, is suggested to be related to neutrophil hyperreactivity with increased neutrophil burst responses also in FILA- B51 transgenic animals. T cell responses to an HLA- B51 derived peptide and its retinal-S antigen homologue in posterior uveitis patients suggest that auto-immune responses might also be relevant. The same peptides are linked to uveitis also in rats and imply that different manifestations of BS may berelated to various and possibly organ-specific antigens.Key Words: Behget’s Syndrome, Immuneresponse